Mass spectrometry is a very sensitive analytical method used for important research and for applications of analytical chemistry, such as life science. A mass spectrometer works by using magnetic and electric fields to exert forces on charged particles (ions) in a vacuum. Therefore, a compound must be charged or ionized to be analyzed by a mass spectrometer. Accordingly, chemical analysis using mass spectrometry involves ionization of molecules in a sample followed by mass analysis of those ions. Typically an ionization source is used to ionize an analyte at atmospheric pressure or inside a vacuum chamber before mass analysis is performed on the produced ions.
Atmosphere based ionization methods involve producing ions at atmospheric pressure and then subsequently transferring those ions into a vacuum chamber that houses a mass analyzer. The ions are then analyzed by the mass analyzer. Examples of such atmosphere based ionization methods include electrospray ionization (Fenn, et al., Science, 1989, 246, 64-71; and Fenn et al., Mass Spectrometry Reviews, 1990, 9, 37-70), and atmospheric pressure chemical ionization (Carroll et al., Analytical Chemistry, 1975, 47, 2369-2373). Recently, ambient ionization methods, including desorption electrospray ionization (Takats et al., Science, 2004, 306, 471-473; Takats et al., U.S. Pat. No. 7,335,897), direct analysis in real time (Cody et al., Analytical Chemistry, 2005, 77, 2297-2302), and others, have been developed to generate analyte ions from complex mixtures for mass analysis. A problem with atmosphere based ionization methods is that the ions from an ion source at atmospheric pressure need to be transferred into vacuum through an atmospheric pressure interface for mass analysis. Generally, the transfer efficiency is 1% or lower.
Methods have been developed in which the sample is ionized within the vacuum chamber, eliminating the need for an ion transfer line. Such methods avoid the ion transfer problems associated with atmosphere ionization methods. Generally, for ionization of an analyte in a vacuum, a photon or electron source, is used to produce a beam of photons or electrons that interacts with the sample in a vacuum chamber. Interaction of the sample with the photons or electrons produces ions that are subsequently analyzed. Exemplary methods include electron impact ionization (Nier et al., Review of Scientific Instruments, 1947, 18, 398-411), laser desorption ionization (Ronald et al., The Rockefeller University, 1989; and U.S. Pat. No. 5,045,694), photo ionization (Lossing et al., The Journal of Chemical Physics, 1956, 25, 1031-1034), chemical ionization (Harrison et al., Ed. Chemical Ionisation Mass Spectrometry; CRC Press, Boca Raton, Fla., 1983), or matrix assisted laser desorption ionization (Karas et al., Analytical Chemistry, 1988, 60, 2299-2301; and Hillenkamp et al., Analytical Chemistry, 1991, 63, 1193A-1203A). Other methods use neutral molecular or ion beams, such as fast atom bombardment ionization (Barber et al., Journal of the Chemical Society, Chemical Communications, 1981, 325-327) and secondary ionization mass spectrometry (Herzog et al., Physical Review, 1949, 76:855-856).